Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus (TIDM) patients who are under intensive insulin therapy increasing the risk for severe hypoglycemia (SH). The consequences of RH are not well understood and its repercussions on neuronal damage and cognitive function after a subsequent episode of SH have been poorly investigated. In the current study, we have addressed this question and observed that previous RH during seven consecutive days exacerbated oxidative damage and neuronal death induced by a subsequent episode of SH accompanied by a short period of coma, in the parietal cortex, the striatum and mainly in the hippocampus...

The detection and processing of novel information encountered in our environment is crucial for proper adaptive behavior and learning. Hippocampus is a prime structure for novelty detection that receives high-level inputs including context information. It is of our interest to understand the mechanisms by which the hippocampus processes contextual information. For this, we performed in vivo microdyalisis in order to monitor extracellular changes in neurotransmitter levels during Object Location Memory (OLM), a behavioral protocol developed to evaluate contextual information processing in recognition memory...

Long-term memories can undergo destabilization/restabilization processes, collectively called reconsolidation. However, the parameters that trigger memory reconsolidation are poorly understood and are a matter of intense investigation. Particularly, memory retrieval is widely held as requisite to initiate reconsolidation. This assumption makes sense since only relevant cues will induce reconsolidation of a specific memory. However, recent studies show that pharmacological inhibition of retrieval does not avoid memory from undergoing reconsolidation, indicating that memory reconsolidation occurs through a process that can be dissociated from retrieval...

The insular cortex (IC) is required for conditioned taste aversion (CTA) retrieval. However, it remains unknown which cortical neurotransmitters levels are modified upon CTA retrieval. Using in vivo microdialysis, we observed that there were clear elevations in extracellular glutamate, norepinephrine, and dopamine in and around the center of the gustatory zone of the IC during CTA retrieval. Additionally, it has been reported that the amygdala-IC interaction is highly involved in CTA memory establishment. Therefore, we evaluated the effects of infusions of an AMPA receptor antagonist (CNQX) and a NMDA receptor antagonist (APV) into the amygdala on CTA retrieval and IC neurotransmitter levels...

It was recently suggested that alteration in lipid raft composition in Alzheimer's disease may lead to perturbations in neurons signalosome, which may help explain the deficits observed in synaptic plasticity mechanisms and long-term memory impairments in AD models. As a first effort to address this issue, we evaluated lipid-raft contents of distinct NMDA and AMPA receptor subunits in the hippocampus of the 3xTg-AD model of Alzheimer's disease. Our results show that compared to controls, 10 months-old 3xTg-AD mice have diminished levels of NMDA receptors in rafts but not in post-synaptic density or total fractions...

Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice...

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder, characterised by the progressive loss of midbrain dopaminergic neurons and a variety of motor symptoms. The gene coding for the phospholipid phosphatase 3, PLPP3 (formerly PPAP2B or LPP3), maps within the PARK10 locus, a region that has been linked with increased risk to late-onset PD. PLPP3 modulates the levels of a range of bioactive lipids controlling fundamental cellular processes within the central nervous system. Here we show that PLPP3 is enriched in astroglial cells of the adult murine ventral midbrain...

During memory retrieval, consolidated memories are expressed and destabilized in order to maintain or update information through a memory reconsolidation process. Despite the key role of the amygdala during memory acquistion and consolidation, the participation of neurotransmitter signals in memory retrieval is poorly understood. Hence, we used conditioned taste aversion and in vivo microdialysis to evaluate changes in glutamate, norepinephrine and dopamine concentrations within the amygdala during memory retrieval...

Dysfunction of synaptic communication in cortical and hippocampal networks has been suggested as one of the neuropathological hallmarks of the early stages of Alzheimer's disease (AD). Also, several lines of evidence have linked disrupted levels of activity-regulated cytoskeletal associated protein (Arc), an immediate early gene product that plays a central role in synaptic plasticity, with AD "synaptopathy". The mapping of Arc expression patterns in brain networks has been extensively used as a marker of memory-relevant neuronal activity history...

The mainstream view on the neurobiological mechanisms underlying memory formation states that memory traces reside on the network of cells activated during initial acquisition that becomes active again upon retrieval (reactivation). These activation and reactivation processes have been called "conjunctive trace." This process implies that singular molecular events must occur during acquisition, strengthening the connection between the implicated cells whose synchronous activity must underlie subsequent reactivations...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by the progressive decline of memory and cognition. Histopathologically, two main hallmarks have been identified in AD: amyloid-β peptide extracellular neuritic plaques and neurofibrillary tangles formed by posttranslational modified tau protein. A definitive diagnosis can only be achieved after the post mortem verification of the histological mentioned alterations. Therefore, the development of biomarkers that allow an early diagnosis and/or predict disease progression is imperative...

Cortical glutamatergic activity is known to be important for memory formation in different learning tasks. For example, glutamate activity in the insular cortex plays an important role in aversive taste memory formation by signaling the unconditioned stimulus. However, the role of glutamate in the insular cortex in appetitive taste learning has remained poorly studied. Therefore, we considered the function of glutamate in attenuation of neophobia, a model of appetitive taste recognition memory. For this purpose, we performed infusions of vehicle, glutamate, a specific mGluR1 antagonist (AIDA) or a combination of glutamate and AIDA at 0 or 30 min, and glutamate or vehicle at 60 min after novel saccharin consumption...

Our current understanding of the neurobiology of taste learning and memory has been greatly facilitated by the use of a reliable behavioural model, conditioned taste aversion (CTA). This model has revealed that the insular cortex (IC), specifically muscarinic and N-methyl-d-aspartate (NMDA) receptor activation in the IC, is critical for the formation of aversive taste memories. In contrast, current models of appetitive taste learning are less adequate, relying on the use of neophobic tastes (attenuation of neophobia) or on the integration of appetitive and aversive taste memories (latent inhibition of CTA)...

In the first part of this review, we will present evidence showing a functional double dissociation between different structures of the medial temporal lobe in the consolidation of object and object-in-context recognition memory. In addition, we will provide evidence to support this differential participation through protein synthesis inhibitors and neurotransmitters antagonists and agonists. This evidence points out that the perirhinal, prefrontal and insular cortices consolidate the information of individual stimuli, i...

Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have been involved in object recognition memory formation, the present study evaluated whether retrieval and reconsolidation are independent processes by manipulating these glutamate receptors...

Alzheimer's disease (AD) is a complex disorder whose etiology is associated with environmental and genetic factors. Recently there have been several attempts to analyze the role of epigenetic alterations in the origin and progression of this neurodegenerative condition. To evaluate the potential participation of the methylation status of the genome that may contribute to AD progression, we have studied the levels and distribution of the 5-methylcytosine and 5-hydroxymethylcytosine in different brain regions at different ages...

There are a number of experiments showing an important involvement of amygdala N-methyl-d-aspartate (NMDA) glutamate receptors on consolidation of conditioned taste aversion (CTA) memory. Interestingly, recent evidence has shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors are particularly involved in CTA retrieval. Memory reconsolidation has been proposed as a destabilization and re-stabilization process induced by memory reactivation. We have recently suggested that reconsolidation could be enabled in the absence of retrieval...

For a long time, the insular cortex (IC) has been related with taste physiology and taste memory processes in animal studies. Recently, the role of the IC has been highlighted by findings involving the IC in non-taste memory formation in both human and animal studies. Recognition memory is based on the ability to assess the familiarity of a previously encountered stimulus, and it is considered a form of declarative memory. In this work, I am proposing that the IC and its related circuitry are highly involved in the conversion of novel to familiar stimulus for both object and taste recognition memory...

Reconsolidation refers to the destabilization/re-stabilization process upon memory reactivation. However, the parameters needed to induce reconsolidation remain unclear. Here we evaluated the capacity of memory retrieval to induce reconsolidation of object recognition memory in rats. To assess whether retrieval is indispensable to trigger reconsolidation, we injected muscimol in the perirhinal cortex to block retrieval, and anisomycin (ani) to impede reconsolidation. We observed that ani impaired reconsolidation in the absence of retrieval...